Penn Study Finds Direct Role for Glial Cells in
Brain Cross-talkFindings may help elucidate mechanisms of wake-sleep transitions
and epileptic seizures

(Philadelphia, PA) - Researchers at the University
of Pennsylvania School of Medicine have demonstrated that star-shaped
glial cells in the brain called astrocytes are directly involved in regulating
communication between neurons. A central finding of the study is that
astrocytes modulate the level of a signaling molecule called adenosine,
which is thought to be important in controlling wake-to-sleep transitions
and epileptic seizures.

“This finding may cause neuroscientists to radically alter their
view of the role of astrocytes as merely supportive to one of actively
communicating with and instructing neurons,” states senior author
Philip G. Haydon, PhD, Professor of Neuroscience. “Astrocytes
are not just the ‘kitchen cells’ of the brain, providing nutritional
support, but instead also help the neurons talk to each other.”
Haydon and colleagues published their results in last week’s issue
of Science.

The central nervous system, which includes the brain and spinal cord,
is composed of specialized cells called neurons that send out and receive
chemical signals called neurotransmitters across a space called the synapse.
This process results in transmission of a nerve impulse. Historically,
the glial cell or astrocyte was considered to be a support cell and to
play no active role in regulating nerve impulse transmission. However,
recent research by Haydon and other investigators has indicated that glial
cells do produce chemical transmitters called gliotransmitters and that
these chemical signals are recognized by the neurons. The studies that
have shown capability were conducted on isolated nerve cells or on slices
of brain tissue.

In this most recent study, the researchers made genetic manipulations
to glial cells in live mice, thus directly demonstrating how astrocytes
function in the brain. The mice were engineered to produce a protein called
SNARE in their astrocytes. When the SNARE protein was produced, the amount
of adenosine decreased.

When adenosine accumulated, nerve impulses were suppressed and could not
be transmitted across the synapse. This helps explain why high adenosine
levels can suppress epileptic seizures.

In contrast, low levels of adenosine increased the transmission of nerve
impulses. The modulation of neuronal activity through the regulation of
the level of adenosine in the synapse may explain the nature of wake-to-sleep
transitions during periods of drowsiness.

“The next step is to study the behavior of these mice during manipulation
of adenosine levels in the brain,” says Haydon.

The study was a collaboration between Haydon and Stephen Moss at Penn
and Ken McCarthy, University of North Carolina, Chapel Hill. The lead
author was Olivier Pascual, a post-doctoral fellow in Penn’s Department
of Neuroscience. Co-authors are Kristi Casper, Cathryn Kubera, Jing Zhang,
Raquel Revilla-Sanchez, Jai-Yoon Sul and HajimeTakano.

This study was funded by the National Institute of Neurological Disorders
and Stroke and the National Institute of Mental Health.

###

PENN Medicine is a $2.7 billion enterprise dedicated
to the related missions of medical education, biomedical research, and
high-quality patient care. PENN Medicine consists of the University of
Pennsylvania School of Medicine (founded in 1765 as the nation's first
medical school) and the University of Pennsylvania Health System.

Penn’s School of Medicine is ranked #2 in the nation for receipt
of NIH research funds; and ranked #4 in the nation in U.S. News &
World Report’s most recent ranking of top research-oriented medical
schools. Supporting 1,400 fulltime faculty and 700 students, the School
of Medicine is recognized worldwide for its superior education and training
of the next generation of physician-scientists and leaders of academic
medicine.

The University of Pennsylvania Health System comprises: its flagship hospital,
the Hospital of the University of Pennsylvania, consistently rated one
of the nation’s “Honor Roll” hospitals by U.S. News
& World Report; Pennsylvania Hospital, the nation's first hospital;
Penn Presbyterian Medical Center; a faculty practice plan; a primary-care
provider network; two multispecialty satellite facilities; and home health
care and hospice.